In most transplant programs, long-term transplant recipients tend to be treated with similar immunosuppressive protocols. However, such uniform treatment may lead to complications from over immunosuppression in some and under immunosuppression in others. Previous studies of withdrawal of one drug have not been successful. An important question is whether an individual immune parameter test or a battery of these tests would best predict long-term graft outcome in stable patients. Retrospective data from individual laboratories has suggested the immune parameters (donor antigen-specific hyporeactivity, allogeneic microchimerism, and the absence of donor antigen-specific HLA antibodies) predict successful long- term outcome after solid organ transplantation. However, each of these parameters has only been applied individuals and only to a subpopulation of transplant recipients. This grant will focus on the use of these three immunologic parameters to predict long-term graft success in a broad transplant population. We will determine whether donor antigen-specific hyporeactivity of the CD4 helped pathway (Specific Aim 1), peripheral blood allogeneic microchimerism (Specific Aim 2), and a lack of development (or regulation of) donor antigen-specific HLA antibodies (Specific Aim 3) correlate with improved long-term graft outcome. We will perform a prospective study, testing all three parameters for lung and heart recipients and the first and third parameters for kidney recipients transplant at the University of Minnesota. The transplant program at the University of Minnesota has a long-established mechanisms for clinical follow-up and clinical data collection. We will determine whether one parameter can be used in lieu of another in an organ specific manner. We plan to use these immune parameters to determine if immunosuppression can be individualized, If so, by selectively lowing immunosuppression in some recipient by maintaining it in others, we will provide significant long- term savings (cost, morbidity and outcome improvement) for solid organ transplant recipients.